We have isolated immune complexes from the cerebrospinal fluid (CSF) of patients with multiple sclerosis. The complexes were dissociated at low pH and run in an analytical isotachophoresis apparatus. In all MS patients, but in no disease or normal controls, we detected a moiety with very high anodal mobility and with an OD254:OD280 ratio greater than 1. These characteristics strongly suggested that the moiety was either DNA, RNA, oligonucleotide or nucleoprotein, and it was referred to as the nucleotide-rich material (NRM). The NRM was presumed to exist in vivo as either an antigen bound to CSF IgG, a small molecule bound non-specifically to IgG or a free molecule with mass similar to that of IgG. The proposed studies will attempt to: 1) Define further the MS specificity of the NRM; 2) Determine whether the NRM contains DNA, RNA or nucleoprotein; 3) Determine whether the NRM exists in the CSF free or complexed to IgG; and 4) Isolate the NRM from CSF or tissues. The major objective of the studies will be to determine whether the NRM is derived from host tissues or from foreign elements, such as a virus. Analytical isotachophoresis will provide the principal assay for the NRM. An electrolyte system and spacer mobility gradient optimum to study the NRM will be developed. The effects on the NRM of DNase, RNase and protease will be assessed. CSF samples will be depleted of immune complexes by absorption with anti-IgG immunoabsorbants and the absorbed CSF examined for residual NRM to determine if the NRM exists in the CSF free or bound to IgG. Isolation of NRM from CSF will depend mainly on preparative isotachophoresis. NRM will be radioiodinated and annealed (molecular hybridization) with cellular DNA extracted from human and various non-human species. If significant homology is found between the NRM and human cellular DNA and this homology exceeds that with non-human DNA, it would seem likely that the NRM is host tissue-derived. If, however, the NRM does not share significant homology with human DNA, we will establish collaborative arrangements to determine whether the NRM does share homology with various viral nucleic acids.